Marrow adiposity has long been identified as a component of the bone marrow micro-environment, although its function, relevance to mineral metabolism and relationship to energy homeostasis has been ignored until recently. Adipocytes originate from a common mesenchymal stem cell that also gives rise to osteoblasts (bone), chondrocytes (cartilage), myocytes (muscle), or stromal (hematopoietic support) cells. Although mesenchymal stem cell allocation dictates that progenitor cells enter only one lineage, there is emerging evidence that marrow adipocyte populations are dynamic, with the capacity to expand or contract in response to genetic, developmental and physiological cues across the lifespan of the animal. In addition, conditions associated with altered metabolism such as aging, diabetes mellitus, glucocorticoid therapy, and anorexia nervosa are all characterized by abnormal accumulation of marrow adipocytes. As such, marrow adipogenesis has been considered neutral, or 'filler'for the marrow space vacated by loss of trabecular bone. However, at the present time, no data exist to define the physiologic role of marrow fat during normal development or relative to energy status. The primary goal of this proposal is to comprehensively plan an inter-disoiplinary approach to define the function of marrow fat relative to energy balance and mineral metabolism. In order to accomplish this, four respected investigators with long-standing interests in skeletal and adipocyte biology will work together to map a strategy for defining physiologic and pathologic aspects of marrow adiposity. This one year "Seeding" grant will enable these scientists to synergize their research efforts using mouse models, metabolomics, structural imaging, molecular biology, and clinical studies for the common purpose of defining experimental paradigms to understand the metabolic paradox of marrow adiposity. We anticipate that at the end of the one-year project the investigators will be well suited to define the process of marrow adipogenesis and its relationship to mineral metabolism. PUBLIC HEALTH RELEVANCE: The long term goal of this proposal is to synergize the efforts of four experts in the fields of bone and adipocyte biology. This group will plan a series of studies that will help define the function of adipose tissue in the bone marrow and its relationship to metabolic disorders such as diabetes mellitus and anorexia nervosa.